RT Journal Article SR Electronic T1 Ser46-Phosphorylated MARCKS Is a Marker of Neurite Degeneration at the Pre-Aggregation Stage in PD/DLB Pathology JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0217-18.2018 DO 10.1523/ENEURO.0217-18.2018 A1 Kyota Fujita A1 Hidenori Homma A1 Kanoh Kondo A1 Masashi Ikuno A1 Hodaka Yamakado A1 Kazuhiko Tagawa A1 Shigeo Murayama A1 Ryosuke Takahashi A1 Hitoshi Okazawa YR 2018 UL http://www.eneuro.org/content/early/2018/08/16/ENEURO.0217-18.2018.abstract AB Phosphorylation of MARCKS (myristoylated alanine-rich C kinase substrate) reflects neurite degeneration at the early stage of Alzheimer’s disease (AD), before extracellular Aβ aggregates are histologically detectable. Here, we demonstrate that similar changes in MARCKS occur in Parkinson’s disease (PD) and dementia with Lewy body (DLB) pathologies in both mouse models and human patients. The increase in the level of pSer46-MARCKS began before α-synuclein aggregate formation, at a time when human α-Syn-BAC-Tg/GBA-hetero-KO mice exhibited no symptoms, and was sustained during aging, consistent with the pattern in human postmortem brains. The results strongly imply a common mechanism of pre-aggregation neurite degeneration in AD and PD/DLB pathologies.Significance Statement: At early stage of Alzheimer’s disease before the aggregation of extracellular Aβ, phosphorylation of MARCKS at Ser46 reflects neurite degeneration. In this study, we confirmed the similar changes both in mouse models and human patients of Parkinson’s Disease (PD) and Dementia with Lewy Bodies (DLB). Phosphorylation of MARCKS at Ser46 was increased before α-synuclein aggregation was detected, and the increase of pSer46-MARCKS was sustained during aging. These results suggest that neurite degeneration detected by pSer46-MARCKS is a common pre-aggregation mechanism shared by AD and PD/DLB pathologies.